结肠癌Caco-2细胞株与患者药靶蛋白表达的一致性研究

目的 对结肠癌细胞株与患者组织间的药物靶点蛋白表达进行一致性研究,以明确两者的相符性。方法 检索Human Protein Atlas数据库中FDA批准的药物靶点蛋白,并对兼有患者结肠癌组织和细胞株数据的蛋白进行表达评分。通过计算蛋白在细胞株与患者间表达的一致率,总体评价两者蛋白表达的相符情况,继而采用生物信息学方法进行蛋白生物学功能和信号通路注释,评价个体患者与细胞株间蛋白表达的差异性。结果 共检索得兼有细胞株（均为Caco-2细胞）和患者表达数据的药物靶点蛋白176个。患者与细胞株表达一致的蛋白比率为57.4%,与患者年龄、性别、肿瘤部位等均无相关性。两者间表达一致性较高或较低的蛋白数分别为69和82,其中47和36个蛋白表达完全一致或完全不一致。不一致蛋白在恶性肿瘤相关通路、免疫相关通路、胞外基质受体相互作用、细胞骨架与形态相关通路的富集更为显著。结论 药物靶点蛋白在Caco-2细胞株与患者结肠癌组织间的表达存在一定的差异性,提示考察细胞株与患者间靶蛋白表达的一致性具有重要意义。

Consistency of the Drug-target Proteins Profile in Human Tumor Tissues and Cell Lines of Colorectal Carcinoma Based on the Human Protein Database

OBJECTIVE To compare the expression level of drug-target proteins in patients'' colorectal carcinoma tissue with Caco-2 cell line from human protein database to clarify the consistency. METHODS The protein expression levels of FDA-approved target-proteins involving in both colorectal carcinoma patients and cell lines were scored base on the intension and quantity of immunohistochemical stain from the database of Human Protein Atlas. And the protein expression between individual and cell line was compared. Then the consistency profiles of total proteins between individual and cell line were evaluated. Ultimately, proteins with well or poor consistent expression were identified analyzed by Gene ontology and KEGG enrichment. RESULTS The expression levels of 176 target proteins involving in both Caco-2 cell line and colorectal carcinoma patients(n=104) were obtained and analyzed. Almost 57.4% of proteins in individual patients were consistent to cell line, which was independently from individual characteristics, such as age, gender and tumor location. About 40% and 47% of total protein, included 47 and 36 proteins with entirely consistent and inconsistent profile, were well and poor consistent expression between patients and cell line, respectively. Those inconsistent proteins were enriched in the pathways related to various types of cancer, immune, extracellular matrix receptor interactions and cytoskeleton. CONCLUSION There is a significant difference in the target protein expression between Caco-2 cell line and colorectal tissue, the results suggest that the consistency is important to investigate cell as the model in drug preclinical development.